The present invention relates generally to radiation delivery systems and more particularly, to a radiation delivery system and method for using the same for brachytherapy of benign, such as neointimal hyperplasia in coronary arteries (restenosis), or malignant proliferative disease.
Restenosis is the recurrence of blood flow obstruction in blood vessels previously treated by percutaneous transluminal coronary angioplasty (PTCA), a medical procedure that improves vascularization of occluded blood vessels using a number of techniques that include catheter-based balloon expansion, stent placement, rotational artherectomy, laser ablation, etc. Although the exact mechanism that results in the production of restenosis is unclear, it is believed to involve neointimal or adventitia hyperplasia (i.e., cell proliferation), vascular recoil, inflammatory processes, or some combination thereof initiated by PTCA. Restenosis is reported to occur in 30 to 50 percent of all PTCA procedures, and follow-up treatment results in increased patient risks, complications, and health care costs (see Tilkian, A. G., and Daily, E. K. Cardiovascular Procedures. Diagnostic Techniques and Therapeutic Procedures. C. V. Mosby Company, St. Louis, Mo. 1986, ISBN 0-8016-4965-X, hereby incorporated by reference).
Intravascular brachytherapy (IVB), a medical procedure involving the delivery of a therapeutic dose of radiation to a tissue portion subsequent to PTCA treatment, shows great promise in reducing the rate of subsequent restenosis.
Typically, a radiation delivery system (RDS) is used for IVB that includes a PTCA catheter-based device such as a stent, balloon catheter, ribbon, wire, etc. that has been modified to include an attached radioactive material. (see Alice K. Jacobs in xe2x80x9cSelection of Guiding Catheters, Practical Angioplasty, David Faxon ed., Raven Press, New York, 1993, hereby incorporated by reference). FIG. 1 shows a process flow chart describing the IVB process. Briefly, the RDS is used it irradiate a lesion following an angioplasty procedure. The RDS is inserted into the guiding catheter and into the body, and passes through the same blood vessels as during the angioplasty procedure. The RDS is positioned near the lesion and allowed to remain there until the radioactive element can provide a therapeutic radiation dose across the lesion.
Results from clinical trials indicate that IVB treatment of blood vessels with a radiation dose of about 15-30 Gray (Gy; 1 Gy=100 rads) significantly reduces the rate of restenosis after PTCA. Table 1 describes several radiation delivery systems that can be used for IVB.
Examples of the coated stent and/or balloon, and the liquid filled balloon, are described in U.S. Pat. No. 5,730,698 to R. E. Fischell entitled xe2x80x9cBalloon Expandable Temporary Radioisotope Stent Systemxe2x80x9d, which issued Mar. 24, 1998. The ""698 patent describes an over-the-wire balloon angioplasty catheter having a balloon surrounded by a reversibly deployable stent system. The balloon can be filled with a radioactive liquid, or the balloon and/or stent can be embedded or implanted with a radioactive material, such as 32p.
Some delivery systems, like the one described in the ""698 patent, involve the insertion and removal of the RDS, while others include a detachable portion, such as a detachable stent, which remains in the body and continues to irradiate tissue after the rest of the device has been removed.
Radiation delivery systems are generally not manufactured at the treatment center, i.e. the hospital, clinic, or the like. This is unfortunate since the most desirable radionuclides cannot be used because they have relatively short half lives (hours) and would decay significantly during shipping. Radiation delivery systems are, therefore, limited to radionuclides with intermediate to long half-lives of days, weeks, or even longer.
Longer lived radionuclides have lower specific activities (SA), and present additional problems with RDS storage, handling and waste disposal. Some beta emitting and gamma emitting radionuclides and their specific activities are listed in Table 2.
There are clear advantages to a RDS that could be produced at or near the treatment center with short lived, high SA radionuclides. Short-lived radionuclides would allow administering the therapeutic dose over a short period of time, minimizing hazards to the patient, hospital workers, and anyone else handling the RDS. In addition, the clinician could select the treatment configuration of the RDS (balloon catheter, stent, guidewire, etc.) and the type of radiation (beta and or gamma radiation) at the treatment center and prepare the RDS immediately prior to use. The RDS geometry could then be based on actual patient parameters, such as the exact length of the lesion and vessel diameter, rather than the manufacturer predetermined parameters necessitated by offsite production.
Therefore, an object of the invention is a radiation delivery system that can deliver an effective dose of radiation to a tissue.
Another object of the invention is a radiation delivery system that can pass through narrow blood vessels.
Another object of the invention is a radiation delivery system that can be uniquely prescribed for a given patient and then manufactured and used at the treatment center.
Another object of the invention is a radiation delivery system that employs short-lived radionuclides with a high specific activity.
Yet another object of the invention is a radiation delivery system that remains intact after delivering a radiation dose to a tissue.
Still another object of the invention is a radiation delivery system that can be used for benign, such as neointimal hyperplasia in coronary arteries (restenosis), and malignant proliferative disease.
Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.
In accordance with the purposes of the present invention, as embodied and broadly described herein, the present invention includes a radiation delivery system that includes a treatment configuration, such as a stent, balloon, ribbon, wire, or the like. The treatment configuration has a surface, at least a portion of which is coated with a layer of gold metal. One embodiment of the invention includes a radiation-emitting self assembled monolayer that is chemisorbed to the gold layer. Another embodiment of the invention includes a radiation-emitting polymer that is chemisorbed to the gold layer.
The invention also includes a method for preparing a radiation delivery system. The process may include providing a treatment configuration, such as a stent, balloon, ribbon, wire, or the like, coating at least a surface portion of the treatment configuration with a gold layer, and allowing a radiation-emitting self-assembled monolayer to form on the gold. A radiation emitting polymer layer can be allowed to form on the gold instead of the self-assembled monolayer.
The invention also includes a method for treating a patient at a treatment center with a radiation delivery system. The method includes determining the treatment configuration and type of radiation required for the patient; preparing a treatment configuration for the patient; covering at least a portion of the treatment configuration with gold; producing radionuclides at the treatment site; allowing a self-assembled monolayer to attach to the gold layer, the monolayer comprising a plurality of organic molecules, wherein each organic molecule has at least one sulfur-containing group, at least one chelating group capable of binding a radionuclide, and at least one radionuclide bound to said chelating group; attaching the radionuclides produced at the treatment center to the chelating group of the monolayer to produce the radiation delivery system; and using the radiation delivery system to deliver a therapeutic dose of radiation to a target tissue in the body.